Hyperglycemia regulates TXNIP/TRX/ROS axis via p38 MAPK and ERK pathways in pancreatic cancer

Wei Li, Zheng Wu, Qingyong Ma, Jiangbo Liu, Qinhong Xu, Liang Han, Wanxing Duan, Yunfu Lv, Fengfei Wang, Katie M. Reindl, Erxi Wu

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Approximately 85% of pancreatic cancer patients suffer from glucose intolerance or even diabetes because high glucose levels can contribute to oxidative stress which promotes tumor development. As one of the reactive oxygen species (ROS)-regulating factors, thioredoxin-interacting protein (TXNIP), is involved in the maintenance of thioredoxin (TRX)-mediated redox regulation. In this study, we demonstrated that high glucose levels increased the expression of TXNIP in time-and concentration-dependent manners and modulated the activity of TRX and ROS production in pancreatic cancer cells, BxPC-3 and Panc-1. We also found that glucose activated both p38 MAPK and ERK pathways and inhibitors of these pathways impaired the TXNIP/TRX/ROS axis. Knockdown of TXNIP restored TRX activity and decreased ROS production under high glucose conditions. Moreover, we observed that the integrated optical density (IOD) of TXNIP staining as well as the protein and mRNA expression levels of TXNIP were higher in the tumor tissues of pancreatic cancer patients with diabetes. Taken together, these results indicate that hyperglycemia-induced TXNIP expression is involved in diabetes-mediated oxidative stress in pancreatic cancer via p38 MAPK and ERK pathways.

Original languageEnglish (US)
Pages (from-to)348-356
Number of pages9
JournalCurrent Cancer Drug Targets
Volume14
Issue number4
DOIs
StatePublished - Jan 1 2014

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Thioredoxins
MAP Kinase Signaling System
p38 Mitogen-Activated Protein Kinases
Pancreatic Neoplasms
Hyperglycemia
Reactive Oxygen Species
Proteins
Glucose
Oxidative Stress
Glucose Intolerance
Oxidation-Reduction
Neoplasms
Maintenance
Staining and Labeling

Keywords

  • Glucose
  • MAPK pathway
  • Pancreatic cancer
  • ROS
  • TXNIP

ASJC Scopus subject areas

  • Oncology
  • Pharmacology
  • Drug Discovery
  • Cancer Research

Cite this

Hyperglycemia regulates TXNIP/TRX/ROS axis via p38 MAPK and ERK pathways in pancreatic cancer. / Li, Wei; Wu, Zheng; Ma, Qingyong; Liu, Jiangbo; Xu, Qinhong; Han, Liang; Duan, Wanxing; Lv, Yunfu; Wang, Fengfei; Reindl, Katie M.; Wu, Erxi.

In: Current Cancer Drug Targets, Vol. 14, No. 4, 01.01.2014, p. 348-356.

Research output: Contribution to journalArticle

Li, Wei ; Wu, Zheng ; Ma, Qingyong ; Liu, Jiangbo ; Xu, Qinhong ; Han, Liang ; Duan, Wanxing ; Lv, Yunfu ; Wang, Fengfei ; Reindl, Katie M. ; Wu, Erxi. / Hyperglycemia regulates TXNIP/TRX/ROS axis via p38 MAPK and ERK pathways in pancreatic cancer. In: Current Cancer Drug Targets. 2014 ; Vol. 14, No. 4. pp. 348-356.
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